1. Field of the Invention
The present invention relates to a method for the treatment of diabetes, which method produces excellent effect of reducing insulin resistance.
2. Background Art
Type II diabetes is a disease exhibiting anomalous glucose tolerance; i.e., high insulin resistance, and the number of patients of diabetes has increased in recent years as a result of lifestyle-related factors such as obesity and overeating. Such patients currently number 7,400,000 in Japan and 150,000,000 throughout the world, and will probably reach 300,000,000 in 2005. Insulin resistance is a state in which insulin-interacting cells exhibit decreased sensitivity to insulin. Increase in insulin resistance is known to cause type II diabetes and have close relation to the onset of hypertension and progress of arteriosclerosis.
Thiazolidines are typical agents which are effective in overcoming insulin resistance. It has been known that when such thiazolidines typified by rosiglitazone or pioglitazone are attached to PPARγ, which is a nuclear receptor, PPARγ is activated, whereby adipose cells are differentiated (J. Biol. Chem. 270, 12953 to 12956 (1995)). However, thiazolidine-based drugs exhibit adverse side effects such as toxicity to the liver, edema, and increase in body weight. Thus, in the treatment of diabetes, a thiazolidine-based drug has been used as an auxiliary medicine to be administered along with a sulfonylurea drug.
In general, diabetes patients often suffer from other diseases. Therefore, reducing or ameliorating insulin resistance is important not only in the treatment of diabetes but also for other pathological conditions. For example, patients of hyperlipemia often exhibit hyperglycemia in relation to insulin resistance. Such patients must be treated for overcoming anomalous lipid metabolism and reducing insulin resistance. As has already been described in literature, α-glycosidase, serving as an oral hypoglycemic agent, remarkably reduces the risk of the onset of heart infarction by virtue of the insulin resistance reduction effect thereof (Lancet, (2002), 359:2072), suggesting that a combined treatment targeting anomalous lipid metabolism and high insulin resistance would be promising treatment. As mentioned above, since thiazolidine-based drugs exhibit adverse side effects such as toxicity to the liver and increase in body weight, other insulin resistance reducing agents that are safer and more effective are demanded in the therapy of hyperlipemia.
Meanwhile, Pitavastatin (i.e., 3-hydroxy-3-methylglutalyl-CoA (HMG-CoA) reductase inhibitor), which is a first choice drug for hyperlipemia (disclosed in JP-B-2569746, U.S. Pat. No. 5,856,336, and EP Patent No. 304063), is known to exhibit an effective blood cholesterol reducing effect in basic research and in clinical settings, as reported in Cardiovasc. Drug Rev. (2003) 21(3), 199 to 215. Meanwhile, pitavastatin exhibits an effect of improving impaired glucose tolerance (insulin resistance reducing effect) in KKAy mice, which are type II diabetes model mice (Therapeutic Research (0289-8020) vol. 24, No. 7, p. 1329-1337 (2003.07)). WO2004/096276 discloses that pravastatin, which is an HMG-CoA reductase inhibitor, also exhibits an effect of reversing impaired glucose tolerance in KKAy mice. However, improvement of the above-obtained effects in overcoming impaired glucose tolerance is still required.
As described above, for the hyperlipemia patients suffering hyperlipemia concomitant with insulin-resistance-related hyperglycemia, in addition to anomalous lipid metabolism, insulin resistance must be properly controlled. However, hitherto, a useful method for the composite treatment of anomalous lipid metabolism and high insulin resistance has never been known.
An object of the present invention is to provide method for treating diabetes having reduced side effect which exhibits excellent ameliorating effect for insulin resistance.